The objectives of this study are to examine changes in subspecies of cytochrome P-450c and P-450d in the rat after treatment with environmental chemicals and to assess the implications of these changes. 1. Induction by a PCB Isomer: Dose response curves and time courses indicate that P-450d are coordinately induced by 3,4,5,3',4',5'-HCB. 2. Methylenedioxyphenyl compounds (MDO) which act as suicide substrates induce different P-450 isozymes. They also differ in their ability to form complexes with different isozymes. Coadministration of methylcholanthrene with MDOs represses induction of P-450b by MDOs at the level of mRNA. 3. Structure-activity relationships of chlorobenzenes as inducers was studied. Hexachlorobenzene is the only 3-MC type inducer. 4. Two constitutive isozymes have been isolated P-450H and P-450G and antibodies raised to these forms. The goal of this project is to better understand the changes occurring in metabolic capability of the liver toward chemical after exposure to environmental chemicals. Antibodies and cDNAs developed to these cytochromes will be used in studying these effects.